Issue

Vol. 35 No. 5 (2023): Vol 35 Issue 5, 2023

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Isoquinoline Containing Azo Schiff Derivatives as Potential Antitubercular Agents: Synthesis, Characterization, Molecular Docking, PASS Prediction and ADME Studies

https://doi.org/10.14233/ajchem.2023.27599
S. Sahana
Department of Chemistry, University College of Science, Tumkur University, Tumakuru-572103, India
https://orcid.org/0009-0001-4109-976X
G.R. Vijayakumar
Department of Chemistry, University College of Science, Tumkur University, Tumakuru-572103, India
https://orcid.org/0000-0002-5894-3250

Corresponding Author(s) : G.R. Vijayakumar

vijaykumargr18@gmail.com

Asian Journal of Chemistry, Vol. 35 No. 5 (2023): Vol 35 Issue 5, 2023

Abstract

A series of isoquinoline containing novel azo Schiff base derivatives (3a-l) were synthesized and characterized by FT-IR, NMR (1H NMR & 13C NMR) and mass spectral analysis. The synthesized title compounds were evaluated for in vitro antitubercular activity against Mycobacterium tuberculosis (MTB) H37Rv strain by microplate alamar blue assay (MABA) method. Among the synthesized series of compounds, the compounds 3a, 3b, 3c and 3d were emerged as excellent antitubercular agents. Compound 3b showed the lowest MIC value of 1.6 µg/mL with a potency equivalent to the standards, isoniazid and ethambutol. Compounds 3a & 3c showed MIC value of 3.125 µg/mL, which is equivalent to the activity of a reference standard pyrazinamide. Compound 3d showed significant activity with MIC of 6.25 µg/mL and other compounds showed good to moderate activity ranging from 12.5 to 50 µg/mL. The four potent components were further tested for in vitro cytotoxicity using MTT assay against MCF-7 and HeLa cell lines to check the selectivity index. Among the tested series, compound 3b possessed the highest cytotoxicity against both MCF-7 (IC50, 7.09 ± 0.41) and HeLa (IC50, 9.04 ± 0.34) cell lines. Additionally, in silico molecular docking was performed to study its binding interaction with Mycobacterium tuberculosis enoyl reductase (InhA) and drug-like features were studied using Swiss ADME tool. PASS analysis of all the compounds showed greater Pa than Pi value for the antituberculosis activity. The results suggested that the synthesized isoquinoline containing azo Schiff base derivatives becomes promising for developing new drugs to treat tuberculosis.

Keywords

Isoquinoline Schiff derivatives Antituberculosis activity Cytotoxicity Molecular docking PASS prediction
Sahana, S., & Vijayakumar, G. (2023). Isoquinoline Containing Azo Schiff Derivatives as Potential Antitubercular Agents: Synthesis, Characterization, Molecular Docking, PASS Prediction and ADME Studies. Asian Journal of Chemistry, 35(5), 1205–1217. https://doi.org/10.14233/ajchem.2023.27599
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX
References
  1. N.R. Gandhi, A. Moll, A.W. Sturm, R. Pawinski, T. Govender, U. Lalloo, K. Zeller, J. Andrews and G. Friedland, Lancet, 368, 1575 (2006); https://doi.org/10.1016/S0140-6736(06)69573-1
  2. World Health Organization, Rapid communication: Key Changes to the Treatment of Drug-Resistant Tuberculosis, Global Tuberculosis Report, Geneva (2022).
  3. R. Johnson, E.M. Streicher, G.E. Louw, R.M. Warren, P.D. Van Helden and T.C. Victor, Curr. Issues Mol. Biol., 8, 97 (2006).
  4. World Health Organization, Catalogue of Mutations in Mycobacterium tuberculosis Complex and their Association with Drug Resistance, Global Tuberculosis Report, Geneva (2021).
  5. K. Mezgebe and E. Mulugeta, RSC Adv., 12, 25932 (2022); https://doi.org/10.1039/d2ra04934a
  6. A. Naqvi, M. Shahnawaaz, A.V. Rao, D.S. Seth and N.K. Sharma, E-J. Chem., 6(s1), S75 (2009); https://doi.org/10.1155/2009/589430
  7. H. Luo, Y. Xia, B. Sun, L. Huang, X. Wang, H.-y. Lou, X. Zhu, W. Pan and X. Zhang, Biochem. Res. Int., 2017, 6257240 (2017); https://doi.org/10.1155/2017/6257240
  8. H. Xu and X. Zeng, Bioorg. Med. Chem. Lett., 20, 4193 (2010); https://doi.org/10.1016/j.bmcl.2010.05.048
  9. G. More, S. Bootwala, S. Shenoy, J. Mascarenhas and K. Aruna, Int. J. Pharma Sci., 9, 3029 (2018); https://doi.org/10.13040/IJPSR.0975-8232.9(7).3029-35
  10. S. Samadhiya and A. Halve, Orient. J. Chem., 17, 119 (2001).
  11. F. Hamon, F. Djedaini-Pilard, F. Barbot and C. Len, Tetrahedron, 65, 10105 (2009); https://doi.org/10.1016/j.tet.2009.08.063
  12. P. Gordon, Nontextile Applications of Dyes, In: The Chemistry and Application of Dyes, Springer, p. 381 (1990).
  13. J. Kunitomo and M. Satoh, Chem. Pharm. Bull., 30, 2659 (1982); https://doi.org/10.1248/cpb.30.2659
  14. X. Zhang, W. Ye, S. Zhao and C.-T. Che, Phytochemistry, 65, 929 (2004); https://doi.org/10.1016/j.phytochem.2003.12.004
  15. E. Corey and D.Y. Gin, Tetrahedron Lett., 37, 7163 (1996); https://doi.org/10.1016/0040-4039(96)01622-X
  16. J.S. Yadav, B.V.S. Reddy, K.S. Raj and A.R. Prasad, Tetrahedron, 59, 1805 (2003); https://doi.org/10.1016/S0040-4020(03)00076-0
  17. Z. Zalán, T.A. Martinek, L. Lázár and F. Fülöp, Tetrahedron, 59, 9117 (2003); https://doi.org/10.1016/j.tet.2003.09.062
  18. J.D. Scott and R.M. Williams, Chem. Rev., 102, 1669 (2002); https://doi.org/10.1021/cr010212u
  19. P. Craig, F. Nabenhauer, P. Williams, E. Macko and J. Toner, J. Am. Chem. Soc., 74, 1316 (1952); https://doi.org/10.1021/ja01125a051
  20. M.C. Francisco, A.L.M. Nasser and L.M. Lopes, Phytochemistry, 62, 1265 (2003); https://doi.org/10.1016/S0031-9422(02)00655-6
  21. H. Kubota, T. Watanabe, A. Kakefuda, N. Masuda, K. Wada, N. Ishii, S. Sakamoto and S. Tsukamoto, Bioorg. Med. Chem., 12, 871 (2004); https://doi.org/10.1016/j.bmc.2003.12.032
  22. A. Hegedüs and Z. Hell, Tetrahedron Lett., 45, 8553 (2004); https://doi.org/10.1016/j.tetlet.2004.09.097
  23. Z.Y. Kadhim, A.N. Seewan, M.T. Abd and H.R. Saud, Int. J. Pharm. Res., 12, 402 (2020); https://doi.org/10.31838/ijpr/2020.12.03.062
  24. L. Collins and S.G. Franzblau, Antimicrob. Agents Chemother., 41, 1004 (1997); https://doi.org/10.1128/AAC.41.5.1004
  25. V.M. Kumbar, M.R. Peram, M.S. Kugaji, T. Shah, S.P. Patil, U.M. Muddapur and K.G. Bhat, Odontology, 109, 18 (2021); https://doi.org/10.1007/s10266-020-00514-y
  26. S. Sahana, G. Vijayakumar, R. Sivakumar, D. Sriram and D. Saiprasad, J. Korean Chem. Soc., 66, 194 (2022); https://doi.org/10.5012/jkcs.2022.66.3.194
  27. A. Daina, O. Michielin and V. Zoete, Sci. Rep., 7, 42717 (2017); https://doi.org/10.1038/srep42717
  28. A. Daina, O. Michielin and V. Zoete, J. Chem. Inf. Model., 54, 3284 (2014); https://doi.org/10.1021/ci500467k
  29. A. Daina and V. Zoete, ChemMedChem, 11, 1117 (2016); https://doi.org/10.1002/cmdc.201600182
  30. D.A. Filimonov and V.V. Poroikov, Bioactive Compounds Design: Possibilities for Industrial Use, BIOS Scientific Publishers: Oxford U.K., p. 47 (1996).
  31. R.K. Goel, D. Singh, A. Lagunin and V. Poroikov, Med. Chem. Res., 20, 1509 (2011); https://doi.org/10.1007/s00044-010-9398-y
  32. N. Khurana, M.P.S. Ishar, A. Gajbhiye and R.K. Goel, Eur. J. Pharmacol., 662, 22 (2011); https://doi.org/10.1016/j.ejphar.2011.04.048
  33. B.S. Furniss, A.J. Hannaferd, V. Rogers, P.W.G. Smith and A.R. Tatchell, Vogel’s Textbook of Practical Organic Chemistry, Longman, Inc.: New York, Edn. 14 p. 716 (1981).
  34. L.-T. Lin, W.-C. Hsu and C.-C. Lin, J. Tradit. Complement. Med., 4, 24 (2014); https://doi.org/10.4103/2225-4110.124335
  35. G. Bickerton, G. Paolini, J. Besnard, S. Muresan and A. Hopkins, Nat. Chem., 4, 90 (2012); https://doi.org/10.1038/nchem.1243
Read More
Author biographies is not available.
Download
AJC-35-5-22
Statistic
Read Counter : 1 Download : 1